The other day, I thought it was about time that I did some of that cool and fancy ResearchBlogging.org stuff, you know, to keep this blog from being nothing more than a collection of not-so-Respectfully Insolent spleen venting at generalized stupidity. I realize that those are some of the funnest posts here and that people like them, but a little variety is required. No study, however, had quite floated my boat, and I was almost to the point of being desperate enough for blog fodder that I considered perusing Age of Autism or even NaturalNews.com (maybe later in the week) in search of that searing stupidity that is always in need of an Insolent takedown. Then what to my wondering eyes should appear (yes, I know Christmas is still two months away) but a study in the British Medical Journal by a group lead by Jon C. Tiburt at the Department of Bioethics at the National Institutes of Health in collaboration with investigators at the Osler Institute at Harvard University and the McClean Center for Clinical Medical Ethics at the University of Chicago entitled Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists.

Serendipity? Who cares? The study addresses a very important aspect of science-based medicine.

In essence, Tiburt et al undertook a survey of 1,200 practicing internists and rheumatologists in the U.S. to assess their usage of placebos and their attitudes towards their use. Their results, summarized in the abstract, are as follows:

679 physicians (57%) responded to the survey. About half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis (46-58%, depending on how the question was phrased). Most physicians (399, 62%) believed the practice to be ethically permissible. Few reported using saline (18, 3%) or sugar pills (12, 2%) as placebo treatments, while large proportions reported using over the counter analgesics (267, 41%) and vitamins (243, 38%) as placebo treatments within the past year. A small but notable proportion of physicians reported using antibiotics (86, 13%) and sedatives (86, 13%) as placebo treatments during the same period. Furthermore, physicians who use placebo treatments most commonly describe them to patients as a potentially beneficial medicine or treatment not typically used for their condition (241, 68%); only rarely do they explicitly describe them as placebos (18, 5%).

There conclusions were:

Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed US internists and rheumatologists. Vitamins and over the counter analgesics are the most commonly used treatments. Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.

Yes, indeed, now there‘s a topic bound to stir up some controversy!
Of course, it did give me pause that fellow ScienceBloggers Abel Pharmboy, Janet Stemwedel, Jake Young, revere, and PalMD had already taken it on. But since when did that ever stop me before? After all, no topic is definitively discussed until it’s given Orac’s loving attention. (Is my ego that big or is this just schtick? You be the judge.)

The placebo effect itself has been discussed before on this blog, of course, and I’ve written numerous posts about how this or that “alternative” medical therapy is really nothing more than an elaborate placebo. (Acupuncture, hypnosis, or homeopathy, anyone?) Fellow skeptical physician Steve Novella gave a good succinct definition the placebo effect as, “any health effect measured after an intervention that is something other than a physiological response to a biologically active treatment. Both Dr. Novella and fellow ScienceBlogger PalMD have pointed out that the placebo effect should more properly be called “placebo effects,” because it is more than just one effect.

As a clinical investigator, I have to deal with issues of the placebo effect all the time. In any clinical trial, especially for symptoms with a subjective component, it is not unusual for the placebo effect to produce an apparent improvement in symptoms in 30% of subjects or more. Indeed, when it comes to science-based medicine, this effect is one reason why less rigorous studies of “alternative medicine” therapies that are arguably nothing more than a placebo (namely homeopathy, which is, after all, nothing more than vigorously shaken water) appear to show efficacy. Indeed, such effects have confounded many a study of “alternative” medical therapies. One thing that has to be emphasized, though. Placebo effects have limits. For example, I am unaware of any study demonstrating that placebo effects prolonged survival in cancer patients or resulted in objectively measurable tumor shrinkage. In this case, arguably the use of placebos is more to blind the investigators to which experimental group the patient is in rather than to provide a true placebo effect. Also, in the case of cancer, it is rarely ethical to use a placebo, as under the Helsinki Declaration, new therapies must be tested against the current standard of care, not a placebo, and it’s rare that there isn’t a standard of care for even metastatic malignancies.

One of the problems with the use of placebo treatments in routine clinical practice outside of the context of a clinical trial is that placebos pose an ethical problem for clinicians. The reason is that their usage inherently requires deception on the part of the physician and makes informed consent by the patient virtually impossible, because if a patient knows that what he or she is receiving is a placebo it might not work.Moreover, as a recent study pointed out, the most robust component influencing the strength of the placebo effect is the patient-practitioner relationship, leading to the question of whether it is an abuse of that relationship for a physician to give a patient something that is not likely to help but either strongly suggest that it will or outright lie and say that it will. On the other hand, placebos can lead to the perception on the part of a patient that his symptoms have improved, and, for conditions where symptoms with a heavy subjective component are what bothers the patient the most, relief of those symptoms is what the patient comes to a physician for. The temptation to try placebos thus becomes especially strong for chronic conditions, where science-based medicine is often less effective in giving the patient what he wants: reliable relief of pain or discomfort. Given these complexities, it’s of interest to learn whether physicians still frequently use placebos. I say “still” because in the past physicians frequently did prescribe placebos to their patients for whom they couldn’t do much else, hoping to harness the power of suggestion and the placebo effect to have the patient think he’s getting better. The attitude was, “What’s the harm?”

Such an activity could be ethically justified in an earlier era, under a medical system in which paternalism was the model upon which most medical practice was built. Indeed, a blogger by the ‘nym revere pointed out that 60 years ago shots of vitamin B12 used to be used widely as an all-purpose placebo good for what ails you. (Of course, since placebos tend to be more powerful the more invasive they are, a shot would be expected to be better at provoking placebo responses than a pill; surgery is the most powerful placebo of all.) Patients were expected to trust their physicians to know and do what was best for them, and physicians were expected to know and do what was best. If a little deception was necessary, so be it. If what was “best” for the patient necessitated withholding a cancer diagnosis because the family didn’t want grandma to know she had advanced cancer, so be it. The problem is that such deception has no place in a model of a physician-patient relationship in which the paternalistic model has become less valid and the role of the physician seen more as collaborative and as an advisor. Society has evolved such that it is now expected that the physician will tell the patient the options and help the patient reach a decision, rather than simply tell the patient what to do. A medical student blogger, Jake Young, has described the current thinking quite well and rejects the use of placebos, while Associate Professor of Philosophy Janet Stemwedel argues that under some circumstances placebo use may be considered ethical.

Does this study help us with this decision? Not a lot. One important aspect of this survey of physicians is how the use of a placebo was defined:

…for the purposes of our research we defined a “placebo treatment” as a treatment whose benefits (in the opinion of the clinician) derive from positive patient expectations and not from the physiological mechanism of the treatment itself.

Another aspect of this study is that Tiburt et al asked about “active” versus “inert” placebos. Inert placebos were placebos not expected to have any activity, such as saline or sugar pills. “Active” placebos were defined as placebos containing an active pharmacological component either unrelated or marginally related to the condition being treated (prescribing antibiotics for viral infections, for example). Finally, although the authors go to great lengths to point out how they used “nonjudgmental” questions and never used the word “placebo” in their survey and how they asked the same question in different ways in order to try to nail down consistency of responses, I’m a bit skeptical that this mattered. Any competent internist or primary care physician–any competent physician–could probably see right through the avoidance of the word “placebo” and discern the purpose of the survey. For example, one question involved a fibromyalgia patient with debilitating pain, about which physicians were asked if they would prescribe a dextrose pill if a study had shown that the dextrose pill produced better subjective relief than no treatment. I’m sorry, but only a medical moron would fail to see through the purpose of this question.

It did not surprise me that few physicians use inert placebos anymore. At least since the time I was in medical school (late 1980s) and probably at least a decade before that, this practice has generally been frowned upon as a violation of patient autonomy and for its introduction of deception into the physician-patient relationship. However, the use of “active” placebos can be even more problematic. According to this survey, active placebos most commonly included:

…over-the-counter analgesics (41%) or vitamins (38%), and some used antibiotics (13%) or sedatives (13%) as placebos.

Using antibiotics as a placebo is profoundly unethical because it violates the precept of primum non nocere, more commonly known as “First, do no harm.” The reason is that it selects for antibiotic resistant bacteria, not only potentially harming the patient but others who might have the patient’s resistant bacteria passed on to them. Prescribing antibiotics for anything other than a documented or strongly suspected bacterial infection is almost always bad medicine. Over-the-counter analgesics can also cause harm in the form of stomach ulcers (nonsteroidal anti-inflamatory drugs) or liver damage (acetominophen). True, the risk is small at the doses recommended, but it is not zero. The same can be said to be true of sedatives. However, the issues surrounding analgesics and sedatives become more complicated because often physicians rationalize their use as also being mildly physiologically effective, thus producing both a “real” pharmacologic response and placebo responses. They might have a point. All therapeutic interventions probably have a placebo component.

Another interesting question is how much of this willingness to prescribe placebos comes from patient demands that the physician “do something.” Such demands are not trivial. Patients come to us as physicians because they have symptoms that are bothering them. We as physicians in general went into medicine to help people and to relieve suffering. It is very hard to say no to a patient. A medical blogger by the ‘nym #1 Dinosaur put it well:

I read the entire article very carefully and discovered that the investigators never asked WHY the respondents recommended the “placebo” treatments that they did. That would have been illuminating. I’ll bet my annual income (ok; big spender I ain’t) that “placebo” prescribing is a response to patient demands to “do something.” I know, I know; we’re supposed to spend whatever time it takes (never fully compensated) to explain to the patient why there is no effective pharmaceutical intervention for their condition (usually after the patient has refused non-pharmacologic modalities like exercise, diet, physical therapy, etc.) Guess what: the patient then goes next door, to one of the 46% of the 57% of the 1,200, who will suggest that they take OTC vitamins or other innocuous compounds, typically describing them not as “placebos” but as “a medicine not typically used for your condition but might benefit you.” Adding insult to injury, the patient usually considers that “placebo prescriber” (the one being unacceptably dishonest) to be a better doctor than the first; the one who follows “advice from the American Medical Association, which recommends doctors use treatments with the full knowledge of their patients,” by refusing to “prescribe placebos” as described in the journal article.

Of course, the vast majority of “alternative” medicine consists of nothing more than elaborate placebos. (And, remember, the more elaborate the placebo, the more likely a placebo effect.) In addition, most “alternative medicine” practitioners give patients exactly what they want and need: Time and an ear to vent to. It’s also not as simple as that in that in any therapeutic encounter there is always likely to be a component of placebo effect, even when the physician prescribes effective medicine.

Finally, one other aspect of this study is relevant for purposes of this blog, and that is how often vitamins and supplements were used as placebos. Abel Pharmboy over at Terra Sigillata makes an excellent point when he wishes that the investigators had delved more into the use of vitamins and supplements as placebos. The reason is that it is not clear whether this category just referred to vitamins or whether it encompassed various herbs and dietary supplements advertised for various purposes, such as Echinacea or glucosamine. What I tend to wonder about along with him is whether the use of dietary supplements for placebo purposes indicates that physicians know that very few such supplements have been shown to be more effective than an “inert” placebo for any condition. Or has the “complementary and alternative medicine” (CAM) movement had its effect, and do many physicians now believe in the efficacy of many of these supplements with little or no evidence of efficacy?

The reason I ask this question is a contrarian one. As it has been pointed out before, the likelihood of placebo effects occuring is maximized when both the patient and the practitioner believe in the efficacy of the treatment being prescribed. Arguably, for purposes of placebo prescribing, the “alternative medical” practitioner would be likely to provide a more effective placebo than the physician who does not believe in (or is at least skeptical of) a given supplement’s likelihood to benefit the patient. After all, if most CAM practitioners really and truly believe in their treatments, believe that they benefit patients, and believe that they work, by whatever mechanism. It doesn’t matter to them whether the mechanism is wildly, outrageously improbable, as it is for homeopathy. It only matters that they believe it, and they do. Compared to CAM practitioners, practitioners of science-based medicine are incompetent at prescribing placebos.

The bottom line to me is that I have a grave ethical difficulties when it comes to placebo use outside the context of a clinical trial. Unless I become a true believing CAM practitioner, the use of placebos would involve my telling patients something that I don’t believe, and, like Jake Young, that is something I simply don’t see myself ever feeling comfortable doing.

Comments

Interesting post, but I still wonder:
If it makes the patient feel better and relieves symptoms, doesn’t this count for *more* than his ability to make “autonomous decisions”, especially in a case where the is actually nothing to chose autonomously cause there is no treatment.

I’ll phrase this in a nasty way (and apologise in advance – I’m not trying to troll, I’m really wondering): Is a doctors reluctance to prescribe placebos for the good of the patient or for the good of the doctor (because *he*/*she* considers it unethically)? And if it is at least partly or mainly the latter, how is this different from a doctor who does not prescribe birth control pills due to his/her moral beliefs?

I am happy to inform physicians who prescribe placebos that I am coming out with an
extra strength Placebo ER (extended release) that will be even more therapeutically
effective.
However, I do object to the use of placebos when a pharmaceutical company produces
studies to the FDA that their new drug is prescription safe and therapeutically more
effective than a placebo. The FDA should not grant approval unless the new drug is
significantly more effective than existing drugs. New drugs are not necessarily better drugs and can be more expensive.

Having been invovled in a number of clinical studies – in which placebos were used – I am deeply disturbed by the results of this study.

In clinical trials – as Orac has already mentioned – the participants know that there is a chance that they will receive a placebo. They have given their informed consent to this chance.

Giving a patient a placebo in response to their demand to “do something” may seem harmless, even prudent and efficaceous, but it is a serious breach of trust.

By giving a placebo, the doctor is lying to the patient. Sure, it seems like a fairly harmless lie – more of a “fib” than a lie – but what happens if the patient discovers the lie?

Once the patient discovers that their doctor is lying to them – that they treated their honestly-expressed concerns with a dishonest placebo – they will have a tinge of distrust in all of their future dealings with that physician. “Is he taking me seriously? Is this a real treatment or is he just trying to get me out of the office?”

If the patient decides to leave the physician’s practice because of this lie, they then face the job of finding another physician, getting an appointment, getting records transferred, etc. This may not be such a problem to a twenty-something with few or no medical problems, but for the average patient of a rheumatologist, it is a daunting prospect.

As I see it, the preservation of trust between the doctor and patient is important for both parties. Arguably, it may be more important to the patient that their doctor maintain their trust.

Prescribing a drug that can produce side effects while knowing it won’t do anything helpful is unethical in my opinion. Prescribing saline oder sugar pills is basically senseless. Besides the ethical concerns you already pointed out I find it at least inept to condition patients on taking pills for symptomatic relief (because if they learn that there will be a pill prescribed for everything, they stop doing all that lifestyle-changing-stuff).
There is a pretty huge reservoir of placebos one can use without too much ethical concerns: the good old household remedies. Instead of prescribing a pill one could send a patient with the common cold home advising him to please drink at least 1 liter of nice, hot tea made from thyme per day, eat chicken soup for dinner, get 8 hours of sleep per night and inhale some essential oil stuff from a bowl with hot water. Oh, and wear a scarf all the time. Such advice written down nicely on a prescription form would please most of the “YOU are the doctor, tell me what I have to do”-crowd.
I work as a nurse help and non-pharmaceutical placebos like a hot-water-bottle, tremendous amounts of hot tea and the like work wonders for most patients.
I think most patients long for the feeling of being taken care of and “mommy-remedies” meet this need (I think it might even work better than some pill).

I think the argument is that the damage done to the doctor-patient relationship by the deception inherent in perscription of a placebos is worse than the benefit due to the placebo effect.
This is made worse when the “placebo” treatment actually has a potentially negative effect (antibiotics or even asprin).

I’ll phrase this in a nasty way (and apologise in advance – I’m not trying to troll, I’m really wondering): Is a doctors reluctance to prescribe placebos for the good of the patient or for the good of the doctor (because *he*/*she* considers it unethically)? And if it is at least partly or mainly the latter, how is this different from a doctor who does not prescribe birth control pills due to his/her moral beliefs?

What Prometeus said. In today’s world, at least in western countries, the doctor is no god (it is different, from what I’ve heard, in very poor and uneducated populations, like, for example, small villages of India).

Many patients are educated and able to get information on their illnesses. If I caught my doctor lying to me in that way, even for my “own good”, I would be deeply disappointed and insulted. It is very demeaning to be sort of told indirectly that you are not smart or strong enough (or that you’re being too “hysterical”) to understand the truth. I just might change doctors to get one who’s at least honest with me. But then, I’m quite partial to the truth, even if told bluntly, and I despise being coddled like a little child.

I doubt if many of the doctors prescribing placebos outright lied to their patients. There are many ways to shade the truth: “Some patients say this works for them, although I don’t see how. But you might want to try it and see if it works for you.” This is probably the rationale for prescribing vitamins–a little extra nutrition (as long as they avoid megadoses) can’t hurt, and what studies have shown definitively that they don’t help? (well, for vitamin C, quite a few, but that is an exception).

I agree that an antibiotic makes a poor placebo because of the potential for side effects and breeding resistant strains, not to mention the cost. On the other hand, some people are dead set on getting antibiotics; people from some parts of the world regard antibiotics as sort of a generalized tonic. And if a condition might be bacterial, I can understand a doctor responding to a patient’s insistence, particularly if it is clear that they are going to find somebody who will give them something and call it an antibiotic.

The big problem with “shading the truth” is that the effectiveness of the placebo and the doctor’s honesty are inversely correlated. The suggestion made is pretty weak and will lead to a weak placebo effect. Put another way, making it work better requires increasing the amount of dishonesty involved.

Also relevant is the fact that saying something technically true, and phrasing it with the deliberate intent to mislead, is not much different than lying. It’ll certainly do similar damage to the doctor-patient relationship.

I hate to say it but patients bring it on themselves by demanding treatments, cures, and therapies that may not even exist. Medicine is a business and doctors have compete in a free market with woo masters, Jenny McCarthys, and other clowns promising all manner of magic.

Sometimes knowing something is being done has a positive effect. The knowledge eases stress, and stress tends to make things worse. At the same time there are occasions when the placebo seems to work better than the medication. It could be the interaction between patient and doctor, it could be something else entirely. We’ve got a lot to learn about how the universe works.

“The FDA should not grant approval unless the new drug is
significantly more effective than existing drugs.”

The problem with this is that for many, many diseases, even for those whose mechanisms are reasonably well-characterized, there are some patients who don’t respond to the drug that the majority of the population responds to. E.g. the overwhelming majority of rheumatoid arthritis patients respond to either one of the anti-TNF mAbs or to MTX, but there is a reasonable percentage of patients who don’t respond for whatever reason. If you won’t approve a drug simply because it’s only going to work for, say, 20% of patients, on the grounds that there DO exist drugs that work for 80% of patients, then you’re leaving those 20% in a lot of pain and miserable. Also, as in the case of antibiotic resistance, you need to have a backup ready and waiting in the wings–bacteria can acquire resistance a LOT faster than we can execute a series of clinical trials.

I agree that new drugs are way too spendy; I sure wish more clinicians were aware of how their scrips affect patients financially, and considered that when choosing a therapy. I’ve seen and heard clinicians lecturing old folks about the importance of compliance, not realizing that the old folks simply could not afford the medications they were being prescribed, but were too humiliated to discuss money issues with their doctor.

So, let me understand: According to this site, it seems that western doctors join the cadre of CAM practitioners in practicing woo, by regularly charging patients for treatments that are proven to have no efficacy. Even worse, the use of active placebos (unlike a harmless homeopathic remedies as you continually point out) like anti-biotics can have effects detrimental to the outcome intended.

The only difference is that perhaps the western medical doctors practise this woo less often. On the other hand, they don’t believe in the treatment compared to CAM practitioners many of whom believe it — making the placebo and desired outcome more effective — but actually extensively study the modes by which these “placebo” effects work best (evidence based).

And yet, I didn’t see a single application of the word “woo” or “crank”, or any derogatory term — a great improvement for this blog.

Kind of cuts the legs out from under years of trying to convince people western medicine is purely evidence based or even self correcting. No wonder it took you so long to comment on this one. I’ll bet doctors have been playing with placebo for as long as the profession existed, and yet, the practise is still prevalent today. It’s even worse today, because in the past, they may have even believed it.

It did not surprise me that few physicians use inert placebos anymore. At least since the time I was in medical school (late 1980s) and probably at least a decade before that, this practice has generally been frowned upon as a violation of patient autonomy and for its introduction of deception into the physician-patient relationship.

Using an inert placebo is no more deceptive than using an unneeded vitamin. You do not need to lie to the patient. If you say, “Studies have shown that this medicine has helped many people with your medical problem,” you have not deceived your patient or violated his ‘autonomy’ (whatever that means). When you have a patient with no disease or a self-limited disease who absolutely believes (due to ignorance, misinformation, or mental illness) that he needs a drug to get well, then prescribing an inert placebo is more ethical than prescribing an active drug or refusing to write a prescription.

I’ve often felt that medical ethicists get too caught up in their concept of ‘a perfect ethic’ and forget that physicians have to treat imperfect patients in nonideal situations.

Schwartz deliberately misreads what was written about placebos. Placebos are known to work. That’s why drug trials are conducted using placebos: we need to know whether the drugs work better than placebos. The situations where placebos are prescribed by physicians are few. 1. A patient with no medical problem believes he is ill, and his perceived symptoms are bothersome. Ideally, this person would be referred to a psychiatrist or psychologist. That isn’t always possible, so prescribing a placebo may be the next best choice. 2. A patient has a real illness that will go away on its own, but the patient absolutely believes that medicines are needed. He is so agitated about the thought of no treatment, that prescribing a placebo now becomes the best treatment for his agitation.

Physicians do not prescribe placebos for conditions that should be treated with active drugs. That would be unethical and stupid (and is what the quacks and woo artists do continually).

I misread nothing. This blog site goes on ad infinitum about how most of the CAM therapies are nothing but placebo compared to western doctors who only use evidence based medicine. This is despite demonstrated efficacy of such placebo in many cases.

It is interesting that you seem to assume a broad based brush at how all CAM practitioners avoid using western medicine at the expense of the health of the patient, yet assume all placebo use by doctors is beneficial.

All broad based assumptions without backup. Not really evidence based any more.

CAM people actually think those treatments will work with a lot of diseases, and treats it even with diseases that would be unrealistic to be treated with placebos, which is a whole lot of diseases. And as Dr. T says, doctors don’t prescribe placebos for diseases that need active agents to work, while the CAM people do. So, he does not think that all use of placebos are good, and only in certain situations should they be used. Therefore, your argument that he thinks that all placebo use for doctor is beneficial is a distortion, Schwartz.

“Physicians do not prescribe placebos for conditions that should be treated with active drugs.”

General statement. Implies no doctors ever prescribe placebos when condition should be treated with active drugs. Given that enormous numbers of people are killed due to errors in prescription or misdiagnosis, this assumption is probably flawed.

“(and is what the quacks and woo artists do continually)”

Since he is responding to my post (where I referred to CAM practitioners) and he’s doing it on this site which feels all CAM practitioners are woo artists, this is also read as a general statement. It assumes all CAM practitioners prescribe placebo at times when active drugs should be used. Another false generalization.

Regarding the TNF and MTX comments–and its related to antibiotics. Most patients respond to MTX, 80%, and the insurance co’s make you take MTX before paying for the spendy TNFs. So once MTX isn’t enough they add a TNF, and you cycle through them hoping to find one that works for a long time. Its not like you are on two TNFs. Its not like its either MTX or TNF, in fact most of the TNFs work best with MTX. It will be great, the day they discover a blood test to figure out which one works before hand. It will save people joint damage and money. Doctors do have preferences and who knows if its the sales people and money making (two TNFs are IV office procedures) or just what they guess will work best. My doctor thinks of my finances, I usually only get liver function tests and that is all I need.

Its interesting to me that they interviewed Internists and Rhuematologists and that antibiotics are mentioned as a placebo. There are woo groups that promote antibiotics as a cure/remission inducer, specifically the tetracyclines for rheumatoid arthritis. There are people on them, that are also on MTX and other DMARDs and think the antibiotic is the one that is helping them. They don’t get off the MTX, or Enbrel or Rituxin and take the antibiotic with them. Despite the fact they are on other DMARDs they continue to promote antibiotic use as the reason they are doing well. To me, I think the reason antibiotics are listed as a placebo is because the patient insists. They give it to them along with MTX, doctor happy, patient happy. Their theory is that a bacteria causes the inflammation and the antibiotic stops it. So I am guessing that many of the antibiotic placebos are the tetraclyclines for RA. Anyway to tell?

Not to pick nits, but placebos don’t work. That’s the whole point of a placebo.

People who receive placebos may get better spontaneously, or they may experience reduced anxiety thinking that they are getting treatment for their medical problem, or they may have sujective complaints that improve because of a variety of reasons having everything to do with their perceptions and nothing to do with the placebo.

I think that it’s very important to keep that in mind – the placebo does nothing. If you give a placebo to a person without their knowledge (slipped into their tea), it doesn’t “work”. The “placebo effect” is part random events (the patient was going to get better anyway) and part psychological (“I feel better now that I’m getting treatment.”).

Since you’re picking nits. Give that the Placebo effect is not understood, I find it interesting that you can claim to definitively define the mechanism. You listed some hypothesis yet represent it as fact?

A Placebo certainly “works” if you are measuring the endpoint which is patient improvement or recovery based on treatment by placebo.

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